rs3895234

chr11-35306278-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004171.4(SLC1A2):c.562-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,557,256 control chromosomes in the GnomAD database, including 47,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3993 hom., cov: 31)
  • Exomes 𝑓: 0.24 (43157 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.03

Genes affected

SLC1A2 (HGNC:10940): (solute carrier family 1 member 2) This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-35306278-A-G is Benign according to our data. Variant chr11-35306278-A-G is described in ClinVar as [Benign]. Clinvar id is 1332976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.562-36T>C		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.562-36T>C		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33222 AN: 151680 Hom.: 3976 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.237 AC: 56272 AN: 237210 Hom.: 7151 AF XY: 0.230 AC XY: 29622 AN XY: 128534

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.107

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.254

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.243 AC: 341855 AN: 1405460 Hom.: 43157 Cov.: 22 AF XY: 0.239 AC XY: 166602 AN XY: 697576

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.219 AC: 33268 AN: 151796 Hom.: 3993 Cov.: 31 AF XY: 0.221 AC XY: 16368 AN XY: 74166

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.0912

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.221

Alfa AF: 0.228 Hom.: 748

Bravo AF: 0.216

Asia WGS AF: 0.187 AC: 648 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 41 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.098
Dann	Benign	0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3895234; hg19: chr11-35327825; COSMIC: COSV53519634; COSMIC: COSV53519634;